Alterations in Acrolein Metabolism Contribute to Alzheimer’s Disease

Article type: Research Article

Authors: Tsou, Han-Hsing^a | Hsu, Wen-Chin^b | Fuh, Jong-Ling^{c; d; e} | Chen, Shih-Pin^{c; d; e; f} | Liu, Tsung-Yun^{a; g} | Wang, Hsiang-Tsui^{b; *}

Affiliations: [a] Institute of Environmental and Occupational Health Sciences, National Yang-Ming University, Taipei, Taiwan | [b] Department of Pharmacology, National Yang-Ming University, Taipei, Taiwan | [c] Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan | [d] Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan | [e] Brain Research Center, National Yang-Ming University, Taipei, Taiwan | [f] Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan | [g] Institute of Food Safety and Health Risk Assessment, National Yang-Ming University, Taipei, Taiwan

Correspondence: [*] Correspondence to: Hsiang-Tsui Wang, No.155, Sec.2, Linong Street, Taipei, 112 Taiwan (ROC). Tel.: +886 02 2826 7097; E-mail: [email protected].

Abstract: Alzheimer’s disease (AD) is a detrimental neurodegenerative disease, and early diagnosis appears to be the key to successful treatment. Acrolein, a byproduct of lipid peroxidation, has been shown to contribute to the pathological process of AD. This study recruited 118 elderly subjects consisting of 58 non-demented control subjects and 62 AD patients. We analyzed the acrolein-related metabolites in the plasma, cerebrospinal fluid (CSF), and urine of all subjects. We found that the levels of acrolein-conjugated protein (Acr-PC) in the plasma (p = 0.00012) and CSF (p = 0.00161) of AD patients were significantly higher than those of control subjects, whereas the levels of a urinary acrolein metabolite, 3-hydroxypropyl mercapturic acid (3-HPMA), were markedly decreased (p = 0.00882) in AD patients. These data suggest that deregulated acrolein metabolism may be correlated with neuronal damage in AD patients, which might provide further insights into the disease progression and early diagnosis of AD.

Keywords: Acrolein, acrolein-conjugated protein (Acr-PC), Alzheimer’s disease, 3-HPMA

DOI: 10.3233/JAD-170736

Journal: Journal of Alzheimer's Disease, vol. 61, no. 2, pp. 571-580, 2018